The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures.

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment is lacking. Here we asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received the antioxidant CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and either Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: 1) location discrimination reversal (which tests behavior pattern separation and cognitive flexibility, two abilities reliant on the dentate gyrus) and 2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment end (14.25-month post-IRR), neurogenesis was assessed (doublecortin-immunoreactive [DCX+] dentate gyrus neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. Notably, one radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had worse stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice show normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change in neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew's longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.

Measurement of the mechanical stiffness in cyclotorsion of the human eye.

We have measured the stiffness in cyclotorsion of the human eye using a scleral suction contact ring mounted on a shaft fitted with an eddy current motor to provide the torque to turn the eye and a shaft-position-encoder to register the torsion. The relation proved to be almost linear within the measuring range in four subjects with constant slope values of about 0.75, 0.60, 0.55 and 0.45 g . cm/deg. The average, 0.6 g . cm/deg, equals 0.5 g if applied at the radius of the globe. This value is rather low compared to the values obtained by other authors for horizontal eye movements. This may be due to different length-tension characteristics of oblique muscles compared to recti muscles.

beta-Thromboglobulin, platelet production time and pletelet function in vascular disease.

Plasma beta-thromboglobulin (beta TG) levels were measured in 103 healthy controls and 112 patients suffering from either peripheral vascular disease (PVD), or cerebrovascular disease (CVD) or deep vein thrombosis (DVT). Plasma beta TG was significantly elevated in 46 PVD patients and 24 recent DVT patients compared to controls, but did not differ significantly in 18 chronic DVT and 24 old CVD patients. In addition, heparin neutralizing activity (HNA) and platelet aggregation induced by adenosine diphosphate, 1-epinephrine and thrombin were compared in 33 out of the 46 PVD patients to 33 controls. The mean HNA was significantly shorter in the PVD patients than in controls. The rate and extent of platelet aggregation were increased in PVD patients compared to controls, but the difference was not statistically significant. Platelet production time (PPT) was measured in 20 controls, 35 PVD patients, nine chronic DVT and 12 chronic CVD patients; significantly shorter PPT was only observed in 14 patients with advanced PVD compared to controls, suggesting increased platelet consumption in these patients. All four assays (plasma beta TG, HNA, platelet aggregation and PPT) were performed in 25 patients; no correlation between the four tests was found in these patients suggesting that the tests were measuring various aspects of platelet function. These results suggest that in vivo platelet consumption as well as platelet aggregation and 'release reaction' are presumably enhanced in PVD and recent DVT patients and that plasma beta TG and PPT assays may be better and more specific indicators of in vivo platelet activation than in vitro platelet aggregation test.

A modified non-radioisotope method for measurement of platelet production time.

Platelet production time (PPT), based on the measurement of malondialdehyde (MDA) production prior to and after the intake of acetylsalicylic acid (ASA), was determined in 20 healthy subjects. High MDA levels were produced by stimulating platelet lipid peroxidation with arachidonic acid, resulting in a reliable, sensitive and accurate technique. PPT correlated well with platelet survival time measured by 51Cr autologous labelled platelets when both methods were used simultaneously in the same patients. This modified non-radioisotope method might serve as a useful aid in the diagnosis of platelet disorders, thromboembolic diseases associated with increased platelet consumption and for the evaluation of drugs affecting platelet function.

Radionuclide venography in the management of proximal venous occlusion. A comparison with X-ray contrast venography.

Ascending contrast venography often fails to show the proximal venous system when there is co-existing occlusion of femoral or iliac veins. Retrograde and pertrochanteric venography both have severe limitations in terms of invasiveness and reliability. Radionuclide venography (RNV) is suggested as a less invasive alternative. 100 patients were investigated by both RNV and X-ray contrast venography (XRV). There was a 72% overall correlation between two methods of investigation. The proximal definition of XRV was limited in those cases with femoral obstruction. RNV, however gave progressively better views as imaging became more proximal and this was accentuated in the presence of femoral or iliac occlusion. RNV is simple and easy to perform and less invasive than XRV. The definition at calf level is such that it cannot at this stage replace XRV as the standard diagnostic procedure. However, in patients with proximal occlusions it gives more reliable information than that obtainable by ascending contrast venography.

Prophylaxis for postoperative deep-vein thrombosis. Synergistic effect of heparin and dihydroergotamine.

Randomized clinical trials in 300 patients undergoing major abdominal surgery or hip replacement arthroplasty were performed to investigate the efficacy of dihydroergotamine mesylate, heparin calcium, or a combination of dihydroergotamine with heparin in preventing postoperative deep-vein thrombosis (DVT). The diagnosis of DVT was established by an uptake test using fibrinogen labeled with iodine 125; in patients undergoing hip replacement, phlebography was also employed to confirm or refute the presence of isotopic thrombi. The data indicate that the combination of dihydroergotamine and heparin is more effective than heparin or dihydroergotamine alone in preventing DVT.